Simple Peptide‐Tuned Self‐Assembly of Photosensitizers towards Anticancer Photodynamic Therapy

Abstract

Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy in vitro and in vivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light.

A Novel Photosensitizer 31,131-phenylhydrazine -Mppa (BPHM) and Its in Vitro Photodynamic Therapy against HeLa Cells

“…Black columns stand for the cell viability of BPHM experiment groups, red columns stand for the cell viability of Mppa experiment groups, and blue columns for the cell viability of control groups. The control groups (blue columns) treated with different concentrations of BPHM (1,5,10,20,30,40, 50, 60 and 120 µM) without light show high cell viability (>90%), which suggests that BPHM could hardly influence the cancer cell without light. However, the BPHM and Mppa experiment clearly showed that with the increasing concentrations of BPHM and Mppa, the cell viability rate is on the decline, suggesting that both BPHM and Mppa have good cell growth inhibiting ability.…”

“…Cell viability of three groups: BPHM experiment groups (black columns), Mppa experiment groups (red columns) and control groups (blue columns). Each group was cultured with different concentrations of BPHM or Mppa (1,5,10,20,30,40, 50, 60 and 120 µM, 200 µL), cell viability was assessed by MTT assay after 24 h. Statistically significant between BPHM and Mppa experiment groups were performed by t-test, p < 0.05 showed the difference was significant).…”

“…In addition, the cells showed marked red fluorescence after uptake BPHM in cancer cells, which makes the compound a potential agent for medical fluorescence imaging. Considering that BPHM can rapidly enter cells, and possessed the hydrophobic character due to the phenylhydrazine structure, hence it may agglomerate when subjected to aqueous solution and may enters cells at the nano-scale [30][31][32]. In order to investigate how BPHM enters cells (in molecular states or nanoparticles), we performed dynamic light scattering (DLS) measurement in phosphate buffer saline.…”

“…About 10 4 cells per well were seeded into 96-well plates and incubated for 24 h prepared for cytotoxicity assessment. Then, the cells of three experimental groups were rinsed with PBS, and subsequently cultured with different concentrations of BPHM and Mppa (1,5,10,20,30,40, 50, 60 and 120 µM), total volume 200 µL per well), respectively, and then incubated for 4 h followed by exposure to visible light for 10 min (675 nm, 25 J/cm 2 ), and then cultured in the dark for an additional 24 h in DMEM media as described above, 5 % CO 2 and 98% humidity at 37˝C. Cell viability was determined by MTT assay.…”

Synthesis and optimization of ZnPc-loaded biocompatible nanoparticles for efficient photodynamic therapy

“…8 Recently, nanopaticles (NPs) have emerged as ideal delivery systems for transport of hydrophobic ZnPc. [9][10][11] For one thing, nanosized carriers can substantially increase the amount of PSs to target cells; 12 for another, the large surface-to-volume ratio facilitates further conjugation of NPs with function groups or targeting agents, so that to increase biological efficacy. [13][14][15][16] Up to now, ZnPc molecules have been encapsulated into various NPs such as liposome, 15,17 polymeric micelles, 18,19 lipid micelles 20 , silica 21 and mesoporous silica NPs 22 , or covalently grafted to NPs, 23 in the form of nanophotosensitizers, for in vitro and/or in vivo PDT.…”